The present invention relates to 3-(4-fluorophenoxy)propionitrile having the formula (I): ##STR3## and a process for preparing the same. The present invention also relates to a process for preparing 6-fluoro-4-chromanone having the formula (II): ##STR4## starting from 3-(4-fluorophenoxy)propionitrile having the formula (I).
6-Fluoro-4-chromanone having the formula (II) is an important intermediate for synthesis of (S)-2,3-dihydro-6-fluoro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'-d ione (USAN: sorbinil) having the formula (III): ##STR5## which is expected to be a novel remedy for a complication of diabetes based on the high activity of aldose reductase inhibition, and can be easily converted into (RS)-2,3-dihydro-6-fluoro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'- dione by Bucherer reaction where the reaction is carried out with heating in the presence of sodium cyanide and ammonium carbonate. 3-(4-Fluorophenoxy)propionitrile is a useful intermediate for synthesis of said 6-fluoro-4-chromanone. Similar compounds such as 3-phenoxypropionitrile, 3-(4-chlorophenoxy)propionitrile and 3-(4-tolyloxy)propionitrile have been known except the compound of the present invention.
Hitherto, 6-fluoro-4-chromanone having the formula (II) has been prepared by Williamson's synthesis, i.e. reacting 4-fluorophenol and 3-chloropropionic acid in the presence of sodium hydroxide to form 3-(4-fluorophenoxy)propionic acid having the formula (IV), which is then warmed in polyphosphoric acid (U.S. Pat. No. 4,117,230 and U.S. Pat. No. 4,130,714). The process is shown in the following scheme: ##STR6##
However, side reaction where 3-chloropropionic acid is decomposed into 3-hydroxypropionic acid exceed the formation of 3-(4-fluorophenoxy)propionic acid having the formula (IV) from 4-fluorophenol and therefore yield of the compound (IV) is still quite low even if great excess of 3-chloropropionic acid is employed (J. Amer. Chem. Soc., 81, 94 (1959)). Thus, the above process cannot be effective for an industrial production of 6-fluoro-4-chromanone having the formula (II), considering a high price of 4-fluorophenol as a starting material.
As the result of the continuous efforts of the present inventors to establish a novel, economical, easily operated and safe process for an industrial production of 6-fluoro-4-chromanone having the formula (II), it was found that 6-fluoro-4-chromanone having the formula (II) could be effectively synthesized by a formation of ether linkage due to cyanoethylation reaction where 4-fluorophenol is reacted with acrylonitrile in the presence of catalyst to give 3-(4-fluorophenoxy)propionitrile having the formula (I), which is either converted into 6-fluoro-4-chromanimine having the formula (V) in polyphosphoric acid and then hydrolyzed, or first subjected to acid hydrolysis to form 3-(4-fluorophenoxy)propionic acid having the formula (IV) and then dehydrated to cyclize in mineral acid such as polyphosphoric acid.
Hitherto, cyanoethylation of phenolic compounds has been carried out in the presence of strong base such as trimethylbenzylammonium hydroxide (Triton B), metallic sodium and sodium methoxide (J. Chem. Soc., 920 (1945), J. Amer, Chem. Soc., 70, 599 (1948), Bull. Soc. Chim. France, 1288 (1957), and the like), in the presence of copper compounds (U.S. Pat. No. 2,974,160) or in the presence of anhydrous aluminum chloride-dried HCl (J. Org. Chem, 22, 1264 (1957)).
As the result of the continuous efforts of the present inventors to establish catalysts effective in the reaction between 4-fluorophenol and acrylonitrile, it was found that copper compounds, especially cupric hydroxide, cupric acetate monohydrate, and the like were excellent catalysts and organic amine, which has not been described as catalyst of cyanoethylation reaction, especially tertiary amine such as triethylamine also could be a particularly effective catalyst in this reaction. Further, it was found that thus obtained 3-(4-fluorophenoxy)propionitrile having the formula (I) could be effectively utilized for a synthesis of 6-fluoro-4-chromanone having the formula (II).